Alterations of epithelial cell physiology are known to result from pathologic mechanisms which occur during periodontal diseases. Of primary clinical importance is the loss of epithelial association with underlying extracellular matrix, adjacent to both hard and soft tissues. There is little understanding of the epithelial cell-substrate attachment mechanism, and this application's broad, long-term objective is to elucidate the role of glycosaminoglycans/proteoglycans (GAG/PG) in the adhesion process. Since GAG/PG regulate important biological processes in many tissues, any alterations in their production, expression and/or relative compositions could affect periodontal physiology; in this regard, it has already been shown that gingival connective tissue GAG/PG composition is altered during inflammation. The hypothesis of this grant application is that chronically inflamed human gingival epithelial cells have altered GAG/PG production which is associated with changes in cell adherence and also proliferation. This hypothesis will be tested in vitro: (1) by first culturing epithelial cells from inflamed and non-inflamed tissues; (2) by then ascertaining whether the two cell groups differ with respect to GAG/PG production; (3) by determining whether the two cell groups manifest differences in attachment as well as proliferation rate, replicative lifespan and viability; and (4) by correlating the functional differences between the two cell groups (i.e., (3) ) with changes in GAG/PG production (i.e., (2) ). A quantitative approach for studying human gingival epithelial cells in vitro, that specifically deals with the confounding issues of patient and experimental variabilities, will be used to accomplish these four specific aims. Pilot data obtained since the last submission indicate the feasibility of this proposal. The proposed research is relevant, clinically, because of the critical importance of dento-epithelial and epithelial-mesenchymal interactions in both health and disease. This investigation is significant, biologically, because the determination of structure-function relationships for proteoglycans is a presently expanding, very exciting area of general cell biology. The results of the proposed studies are expected to contribute to current understanding of periodontal biology.